Market Report Source

Overview

Introduction
Systemic Lupus Erythematosus is a chronic, life-long and potentially fatal autoimmune disease characterized by multiple system distress and unpredictable flares. High unmet need makes this an attractive market but dispute over patient numbers and clinical trial difficulties are significant hurdles for new entrants to overcome.

Scope
Assessment of patient size across the seven major markets (US, Japan, France, Germany, Italy, Spain, UK), including split by age and gender
Qualitative interviews with key opinion leaders including treating physicians, patient advocates and research scientists
Investigation of the current unmet needs from a range of professionals involved in SLE treatment and research
Current treatment controversies and novel therapies in the developmental pipeline

Highlights
The main obstacle to approval of a new treatment for SLE is ambiguity in the requirements for randomized clinical trials. Recruitment is becoming a particular issue as a large number of late-Phase trials are being carried out at present. Datamonitor recommends e-recruitment, patient advocacy group collaboration and liaison with regulatory agencies.

Awareness among primary care physicians is low, but once a treatment reaches the market, companies are expected implement large marketing initiatives. This will to improve physician knowledge of the condition and available treatments, aiding the challenge of correct diagnosis of this disease, and enlarging the market.

New drugs entering the market have a number of opportunities which can be exploited by the developing company. Orphan drug status is a key advantage of the SLE market. However, improved SLE survival rates have emphasized co-morbidities, resulting in the threat of an increased risk of thrombotic events.

Reasons to Purchase
Identify the challenges in clinical trial design including assessment tool selection and renal verses non-renal designs
Understand the key issues for potential treatments for heterogeneous SLE patients
Gain insight into opinion leaders’ thoughts on the challenges facing the SLE market

Table of Contents

About the CNS, Arthritis and Pain pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Datamonitor insight into the lupus market

CHAPTER 2 INTRODUCTION AND EPIDEMIOLOGY

Classifications

Diagnosis and severity – the “Chameleon” disease

Cutaneous or discoid lupus

Neuropsychiatric and CNS involvement in SLE

Neonatal lupus erythematosus

Drug-induced lupus erythematosus

Raynaud’s phenomenon

Epidemiology of SLE

Datamonitor estimates a conservative SLE patient number

US SLE population is estimated between 200,000 and 1.5 million

European SLE demographics benefit from Euro-Lupus study but population estimate is indistinct

Japanese SLE population is especially difficult to estimate as data is rare

Improved SLE survival rates are increasing prevalence

Late morbidity risk increases as patients live longer

Genetic influences are key in SLE epidemiology

Race and ethnic segmentation – nature vs. nurture

Other suggested risk factors include environmental factors

CHAPTER 3 CURRENT TREATMENT

Treatment algorithms vary with disease type

Non-pharmacological treatment largely involves education and avoidence of flare triggers

Pharmacological treatment currently revolves around steroids antimalarials and cytotoxic agents

Prednisone and Hydroxychloroquine are the mainstay of SLE treatment

Lupus nephritis is a key patient segment

Non-renal lupus includes joint, skin and CNS manifestations

Joint involvement

Dermatological involvement

CNS involvement and Neuropsychiatric (NP) symptoms

CHAPTER 4 ASSESSMENT AND CLINICAL TRIAL DESIGN

Assessment criteria vary in popularity and usefulness in certain aspects of the disease

Systemic Lupus Erythematosus Activity Index (SLAM)

SLICC/ACR Damage Index

SLE Disease Activity Index (SLEDAI and SLENA-SLEDAI)

The British Isles Lupus Assessment Group (BILAG)

European Consensus Lupus Activity Measure (ECLAM)

Biomarker research aims to find an accurate, easily performed test for outcome or diagnostic purposes

Clinical trial design in SLE is a notoriously difficult task

Key challenges in the study of drug effects in Lupus

Specific trial designs

Dose ranging and Phase IIa and b trials

Disease activity

Superior safety/similar efficacy

Steroid sparing endpoints

Organ specific endpoints

Segmenting by lupus nephritis is a popular design, and invites off-label use in other SLE manifestations

Skin specific segmentation allows approval for a larger percentage of the overall lupus population as most will suffer from skin involvement

CHAPTER 5 INCREASING SLE MARKET OPPORTUNITIES

Awareness is increasing but primary care physicians should be targeted

Misdiagnosis is a problem which is being addressed by the SLICC group

Increasing awareness and diagnosis by improved definition of SLE

Market potential can be based on estimated sales or cost to the healthcare system

Diagnosis value

Cost of SLE to the healthcare system

New treatments should be steroid sparing with a comparable side-effect profile to CellCept

Which cells play a major role in the SLE autoimmune response?

The risk-to-benefit profile in lupus depends on disease severity and the system affected

Orphan drug designation is a key opportunity

FDA requirements

EMEA requirements and possible advantages

Making use of patient advocacy groups and media advertising addresses challenges in clinical trial recruitment

The UK advantage

Recruitment

eRecruitment and making use of the media

Partnering with physican and patient organizations

CHAPTER 6 PIPELINE DRUGS AND KEY TRIALS

Immunosuppressants

CellCept (mycophenolate mofetil)

Arava (leflunomide)

Riquent (abetimus)

B-cell therapy

Rituxan/MabThera (rituximab)

Cost

LymphoStat-B (belimumab)

Epratuzumab

Other cytokines suppression

Actemra (tocilizumab)

Liver enzyme irregularity with MRA is the current concern in both SLE and RA indications

CTLA4-Ig

Orencia (abatacept) – BMS

RG2077 – Repligen

Other pipeline possibilities

Gene therapy

Interferon suppression

DHEA (PrestaraT)

Autologous stem cell transplantation

Discoid and cutaneous lupus erythematosus

Topical immunomodulators – Protopic (tacrolimus) and Elidel (pimecrolimus)

Raptiva (efalizumab)

APPENDIX

Contributing experts

Bibliography

Other sources

Government sites:

News sources:

American College of Rheumatology links:

Company websites:

Patient organizations:

Other

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare’s research and analysis methodologies

Datamonitor Healthcare’s therapy area capabilities

Disclaimer

List of Tables

Table 1: Range and frequency of symptoms associated with Lupus

Table 2: SLE population across the seven major markets, 2006

Table 3: Key SLE epidemiology studies

Table 4: Summary of key disease activity assessment tools

Table 5: WHO lupus nephritis classification, 1982

Table 6: Estimated sales for main drugs used in SLE, $ (000s), 2005

Table 7: Variations in prevalence criteria for orphan drug status

Table 8: Products in clinical development for lupus indications, 2006

Table 9: Actemra (tocilizumab) development schedule in all indications, March 2006

List of Figures

Figure 1: SLE system and general severity range

Figure 2: General treatments used for SLE

Figure 3: The risk and cost verses benefit profile for different severities of lupus symptoms

Figure 4: Geographical comparisons between the major research areas for lupus

Figure 5: Key messages to include when advertising for patient participation 75